scholarly journals Slowing the Loss of Physical Function in Amyotrophic Lateral Sclerosis With Edaravone: Post hoc Analysis of ALSFRS‐R Item Scores in Pivotal Study MCI186 ‐19

2021 ◽  
Author(s):  
Benjamin Rix Brooks ◽  
Erik P. Pioro ◽  
Jonathan Katz ◽  
Fumihiro Takahashi ◽  
Koji Takei ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Physical Function ◽  
Post Hoc Analysis ◽  
Pivotal Study ◽  
Item Scores ◽  
Post Hoc ◽  
Lateral Sclerosis

scholarly journals Plasma exchange with albumin replacement and disease progression in amyotrophic lateral sclerosis: a pilot study

2021 ◽  
Author(s):  
Mónica Povedano ◽  
Andrés Paipa ◽  
Miquel Barceló ◽  
Michael K. Woodward ◽  
Sandra Ortega ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Pilot Study ◽  
Disease Progression ◽  
Plasma Exchange ◽  
Rating Scale ◽  
Open Label ◽  
Primary Endpoints ◽  
Rate Of Decline ◽  
Post Hoc ◽  
Lateral Sclerosis

Abstract Background Plasma exchange (PE) is used to treat a range of neurological disorders. Based on results demonstrated in Alzheimer’s disease, we theorized that PE with albumin replacement (PE-A) might alter the metabolic profile of plasma and cerebrospinal fluid in patients with amyotrophic lateral sclerosis (ALS) by removing disease-inducing molecules. The aim of this study was to evaluate the effect of PE-A on disease progression in ALS. Methods In this open-label, non-controlled, single-arm, prospective pilot study, 13 adults with ALS had 6 months’ treatment with PE-A 5% and 6 months’ follow-up. Primary endpoints were changes from baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC) through 48 weeks. A post hoc analysis compared individual patient data with the expected ALSFRS-R progression slope. Results The median ALSFRS-R score declined throughout the study, although the rate of decline was slower than expected in seven patients at treatment end and in five patients at study end. Six patients remained in the same baseline slope progression category, and four patients improved their slope category at treatment end. Median FVC decreased significantly during the study. Treatment was well tolerated. Of 330 PE-A procedures, 0.9% were associated with potentially related adverse events. Conclusion Although functional impairment progressed, about two-thirds of patients showed a slower than expected rate of decline at treatment end. Most patients had unaltered (54.5%) or reduced (36.4%) ALSFRS-R slope progression at treatment end. Further evaluation of PE-A in controlled studies involving more patients is warranted. EudraCT number 2013-004842-40. Trial registration ClinicalTrials.gov identifier: NCT02479802.

SAT0145 EFFICACY AND SAFETY OF UPADACITINIB MONOTHERAPY IN MTX-NAÏVE PATIENTS WITH EARLY ACTIVE RA RECEIVING TREATMENT WITHIN 3 MONTHS OF DIAGNOSIS: A POST-HOC ANALYSIS OF THE SELECT-EARLY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1011.1-1011
Author(s):  
M. C. Kapetanovic ◽  
M. Andersson ◽  
A. Friedman ◽  
T. Shaw ◽  
Y. Song ◽  
...  
Keyword(s):  
Physical Function ◽  
Symptom Onset ◽  
Joint Damage ◽  
Safety Analysis ◽  
Research Support ◽  
Phase 3 ◽  
Post Hoc Analysis ◽  
Structural Joint ◽  
Safety Outcomes ◽  
Post Hoc

Background:Early treatment of RA within the therapeutic window(0-3 months from symptom onset), has been associated with improved clinical outcomes and physical function. However, ≤42% of RA patients(pts) visit a rheumatologist within 90 days of symptom onset1,2.Objectives:To assess safety and efficacy of Upadacitinib(UPA), an oral, reversible, potent JAK-1 selective inhibitor3, in pts with moderate to severely active RA who were MTX-naïve or had an inadequate response to csDMARDs/bDMARDs4-6.Methods:In SELECT–EARLY, MTX-naïve pts with active RA and poor prognosis were randomized 1:1:1 to once-daily UPA monotherapy at 15 or 30 mg or weekly MTX (titrated up to 20 mg/week through Week 8). Efficacy (including ACR, DAS28(CRP), CDAI responses and change in mTSS) and safety outcomes from a post-hoc analysis of patients who received treatment within 90 days from diagnosis are reported here. The statistical significance defined asp<0.05was exploratory in nature.Results:A total of 270 pts commenced treatment within 90 days from RA diagnosis (median: 44 days [11, 89]). Pts in each arm were mostly female (70%), had moderately to severely active RA with mean DAS28(CRP) =5.9±1.02, had structural joint damage (mean mTSS =7.7±21.5) and were seropositive for both ACPA and RF at baseline (72%)4. At Week 24, compared to MTX, significantly greater proportions of pts receiving UPA 15 or 30 mg monotherapy achieved efficacy outcomes including ACR20, 50 and 70 responses, DAS28CRP<2.6, CDAI≤2.8 or Boolean remission. Improvements in physical function (HAQ-DI) and decrease in pain were also significantly greater in pts receiving UPA 15 and 30 mg vs MTX at Week 24. Treatment with UPA was also associated with a greater inhibition of structural joint damage compared with MTX (Figure 1). Safety outcomes were consistent with the full study and the integrated safety analysis (all phase 3 studies of UPA). Compared to MTX, higher frequencies of serious infections and herpes zoster were reported in both UPA groups. There were 2 deaths in total (UPA 30 mg: 1 due to cardiovascular death and 1 due to pneumonia and sepsis) (Figure 2).Conclusion:In RA pts, early initiation of treatment with UPA 15 mg and 30 mg monotherapy within 3 months from diagnosis was associated with clinically meaningful improvements in efficacy, including remission and inhibition of progression of structural joint damage compared to MTX. The safety profile was consistent with the overall study and the integrated phase 3 safety analysis7. UPA seems to be a promising treatment option for more patients to reach their treatment targets of remission or low disease activity when treated within 3 months of diagnosis.References:[1]Raza K et al. Ann Rheum Dis. 2011;70(10):1822-5.[2]Stack RJ et al. BMJ Open. 2019;9:e024361.[3]Parmentier et al. BMC Rheumatol. 2018;2:23.[4]van Vollenhoven R et al, Arth Rheumatol. 2018; 70 (s10) [Abs ACR2018].[5]Burmester GR et al. Lancet 2018;391:2503-12.[6]Genovese MC et al, Lancet 2018;391:2513-24.[7]Cohen S et al, Ann Rheum Dis [Abs EULAR2019].Disclosure of Interests:Meliha C Kapetanovic: None declared, Maria Andersson Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Tim Shaw Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Ulf Müller-Ladner Speakers bureau: Biogen, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB

Inside minds, beneath diseases: social cognition in amyotrophic lateral sclerosis-frontotemporal spectrum disorder

2020 ◽  
Vol 91 (12) ◽  
pp. 1279-1282
Author(s):  
Patricia Lillo ◽  
Paulo Caramelli ◽  
Gada Musa ◽  
Teresa Parrao ◽  
Ricardo Hughes ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cognitive Impairment ◽  
Social Cognition ◽  
Digit Span ◽  
Short Version ◽  
The Social ◽  
Significant Difference ◽  
Similar Disease ◽  
Post Hoc ◽  
Lateral Sclerosis

ObjectiveTo compare social cognition performance between patients with amyotrophic lateral sclerosis (ALS) and those patients with behavioural variant frontotemporal dementia (bvFTD).MethodsWe included 21 participants with ALS, 20 with bvFTD and 21 healthy controls who underwent a comprehensive cognitive battery, including the short version of the Social Cognition and Emotional Assessment (Mini-SEA), which comprises the faux pas test and Facial Emotion Recognition Test (FERT); Mini-Mental State Examination; Frontal Assessment Battery; lexical fluency (F-A-S), category fluency (animals/minute), digit span (direct and backwards) tests and the Hayling test. A post hoc analysis was conducted with the patients with ALS divided into two subgroups: patients without cognitive impairment (ALScn; n=13) and patients with cognitive impairment (ALSci; n=8).ResultsNo significant difference was noted between participant groups in terms of the age, sex and education. ALS-total group and patients with bvFTD had similar disease durations. Patients with ALSci performed poorly when compared with controls with regard to the FERT (p<0.001), the faux pas (p<0.004) and the Mini-SEA (p<0.002) total scores. Moreover, patients with bvFTD performed poorly in comparison with controls in executive and social cognition tests. The performance of patients with ALSci was similar to that of patients with bvFTD, while the performance of patients with ALScn was similar to that of controls.DiscussionOur findings support a cognitive continuum between ALS and bvFTD and shed light on the cognitive heterogeneity of ALS, expanding its possible neuropsychological profiles.

scholarly journals Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Vibeke Strand ◽  
Jeffrey Kaine ◽  
Rieke Alten ◽  
Gene Wallenstein ◽  
Annette Diehl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Physical Function ◽  
Global Assessment ◽  
Janus Kinase ◽  
Patient Global Assessment ◽  
Normative Values ◽  
Post Hoc Analysis ◽  
Patient Reported ◽  
Post Hoc

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients. Results Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients. Conclusions This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care. Trial registration Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)

scholarly journals Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

Neurology ◽  
2017 ◽  
Vol 89 (18) ◽  
pp. 1915-1922 ◽  
Author(s):  
Ruben P.A. van Eijk ◽  
Ashley R. Jones ◽  
William Sproviero ◽  
Aleksey Shatunov ◽  
Pamela J. Shaw ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Clinical Data ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Lithium Carbonate ◽  
Targeted Treatments ◽  
Individual Participant ◽  
Post Hoc ◽  
Lateral Sclerosis

Objective:To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.Methods:Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype.Results:Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7–1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3–4.3; p = 0.006 and HR 2.5, 95% CI 1.1–5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2–69.1) to 69.7% (95% CI 50.4–96.3).Conclusions:This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.

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